Disease/Drug of interest:Salmonellosis Fig.1 A close-up image of the salmonella bacteria.
Motivation and Background: Salmonellosis is an illness of the digestional tract that people contract from a Salmonella infection. Salmonella is a type of food poisoning and is the leading cause of bacterial foodborne illnesses in the United States. About 1.2 million illnesses are reported in a year due to salmonella infection, but salmonella could actually be the cause of a lot more food poisoning cases than reported because it often occurs without recognition or treatment. Most frequently, Salmonella is found in uncooked eggs and poultry. While these are the more common places to find Salmonella, trace amounts can also be found in a range of other foods such as fruits, vegetables, and many processed foods. In most cases of salmonellosis, the disease is not too serious and people can recover without treatment in a week or so. In some cases, however, salmonella can be very serious, causing many hospitalisations and about 450 deaths in the US every year. Essentially, anyone who eats the foods listed above is subject to contracting salmonellosis, though not everyone is equally susceptible. Young children under the age of 5, elderly people, and those with weaker immune systems are particularly vulnerable to being infected by salmonella. Within 12 to 72 hours of being infected by salmonella, patients contract diarrhea, fever, and abdominal cramps. Most patients recover without antibiotics, but in those who don’t, the salmonella infection can spread from the intestines to the bloodstream. If Salmonella goes untreated once the infection has reached the bloodstream, it can cause death or severe illness. Many prevention practices have been put in place since the discovery of Salmonella, however, Salmonellosis is still a serious disease that affects many more Americans than any other foodborne illness. If the money were to be put towards Salmonellosis, I would suggest it be used to do more extensive research on the drug resistance of the bacteria. This is important because if a drug-resistant strain of salmonella develops, then an epidemic could occur.
References: [1] Salmonella. https://www.cdc.gov/salmonella/index.html (accessed Feb 1, 2017). [2] E. Wintersberger, Regulation and biological function of thymidine kinase. Biochemical Societal Transactions1996, 25, (1), 303-8. [3] Thymidine kinase. https://www.ncbi.nlm.nih.gov/protein/59524 (accessed Feb 1, 2017). [4] Landau, R.; Achilladelis, B.; Scriabine, A., Pharmaceutical Innovation; Chemical Heritage Foundation: Philadelphia, 1999. [5] Ceftriaxone. https://pubchem.ncbi.nlm.nih.gov/compound/5479530#section=Top (accessed Feb 1, 2017). [6] Mar, E. C.; Chiou, J. F.; Cheng, Y. C.; Huang, E. S., Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphates. Journal of Virology1985, 53, (3), 776-780. [7] United States Patent and Trademark Office. www.uspto.gov (accessed Feb 1, 2017). [8] Clinical Trials. www.clinicaltrials.gov(accessed Feb 1, 2017).
Fig. 2 A molecular graphic of the 3D structure of Thymidine Kinase, the blue and the pink portions represent two different molecules, chain a and chain b.
Size: 40930 Daltons
Location: Thymidine kinase (TK) can be found in almost all mammalian cells. Inside a cell, TK is located in the cytoplasm. Thymidine kinase is made during the synthesis phase of the cell cycle. After the protein is produced, it does not disperse throughout the cell initially because it is regulated by an inhibitor called thymidine triphosphate (TTP). Thymidine triphosphate stops the synthesis of thymidine kinase when there is too much of it in the cell. Thymidine kinase is not always present in the cell, it is created when the cell is preparing for division and synthesis.
Function in a normal cell: Thymidine kinase is an important catalyst in the reaction to make thymidine monophosphate. This reaction is represented as: thymidine + ATP ---> thymidine monophosphate + ADP. Thymidine monophosphate goes through another reaction to become thymidine diphosphate, and then another to finally become thymidine triphosphate, the inhibitor of thymidine kinase. The main purpose of these reactions is to introduce thymidine into the DNA, which plays an important role in cell division. Thymidine triphosphate is a required building block for the creation of an extra set of DNA when a cell is preparing to divide.
Drug Information: Ceftriaxone Schematic figure of drug: Fig. 3 The 2D structure of Ceftriaxone. Nitrogen is blue, Sulfur is yellow, Oxygen is red, Carbon and Hydrogen are grey.
Formula: C18H18N8O7S3
Molecular weight: 554.571 g/mol
CAS Number: 73384-59-5
Delivery method: injection into a vein
Side effects: pain at injection site, weakness, pale skin, diarrhea, nausea and vomiting, heartburn, rash, stomach bloating, stomach cramps, hemolytic anemia, gall bladder disease, difficulty swallowing, painful or decreased urination, and seizures
Other names: Rocephin, Epinephrine, Biotrakson
Maker or company: Roche
Is it patented?No
Clinical Trials Info: There have been a few clinical trials testing the efficacy of different drugs on the treatment of Salmonellosis. Studies have also been done on the increasing number of drug-resistant salmonellosis strains.
Origin:This drug is a semisynthetic antibiotic that consists of ceftriaxone sodium and is derived from a fungus called Acremonium.
Alternatives to this drug: Zithromax, Flagyl, Docycycline, Azithromycin
Miscellaneous: Ceftriaxone is more active against gram-negative bacteria than gram-positive bacteria
Other uses: sinus infections, endocarditis, Lyme disease, shigella, relapsing fever, typhoid fever, Whipple’s disease, and to prevent infection in certain penicillin-allergic patients
Fig.1 A close-up image of the salmonella bacteria.
Motivation and Background:
Salmonellosis is an illness of the digestional tract that people contract from a Salmonella infection. Salmonella is a type of food poisoning and is the leading cause of bacterial foodborne illnesses in the United States. About 1.2 million illnesses are reported in a year due to salmonella infection, but salmonella could actually be the cause of a lot more food poisoning cases than reported because it often occurs without recognition or treatment. Most frequently, Salmonella is found in uncooked eggs and poultry. While these are the more common places to find Salmonella, trace amounts can also be found in a range of other foods such as fruits, vegetables, and many processed foods. In most cases of salmonellosis, the disease is not too serious and people can recover without treatment in a week or so. In some cases, however, salmonella can be very serious, causing many hospitalisations and about 450 deaths in the US every year. Essentially, anyone who eats the foods listed above is subject to contracting salmonellosis, though not everyone is equally susceptible. Young children under the age of 5, elderly people, and those with weaker immune systems are particularly vulnerable to being infected by salmonella. Within 12 to 72 hours of being infected by salmonella, patients contract diarrhea, fever, and abdominal cramps. Most patients recover without antibiotics, but in those who don’t, the salmonella infection can spread from the intestines to the bloodstream. If Salmonella goes untreated once the infection has reached the bloodstream, it can cause death or severe illness. Many prevention practices have been put in place since the discovery of Salmonella, however, Salmonellosis is still a serious disease that affects many more Americans than any other foodborne illness. If the money were to be put towards Salmonellosis, I would suggest it be used to do more extensive research on the drug resistance of the bacteria. This is important because if a drug-resistant strain of salmonella develops, then an epidemic could occur.
References:
[1] Salmonella. https://www.cdc.gov/salmonella/index.html (accessed Feb 1, 2017).
[2] E. Wintersberger, Regulation and biological function of thymidine kinase. Biochemical Societal Transactions 1996, 25, (1), 303-8.
[3] Thymidine kinase. https://www.ncbi.nlm.nih.gov/protein/59524 (accessed Feb 1, 2017).
[4] Landau, R.; Achilladelis, B.; Scriabine, A., Pharmaceutical Innovation; Chemical Heritage Foundation: Philadelphia, 1999.
[5] Ceftriaxone. https://pubchem.ncbi.nlm.nih.gov/compound/5479530#section=Top (accessed Feb 1, 2017).
[6] Mar, E. C.; Chiou, J. F.; Cheng, Y. C.; Huang, E. S., Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphates. Journal of Virology 1985, 53, (3), 776-780.
[7] United States Patent and Trademark Office. www.uspto.gov (accessed Feb 1, 2017).
[8] Clinical Trials. www.clinicaltrials.gov(accessed Feb 1, 2017).
External links:
https://www.cdc.gov/salmonella/index.html
https://www.ncbi.nlm.nih.gov/protein/59524
https://pubchem.ncbi.nlm.nih.gov/compound/5479530#section=Top
www.uspto.gov
www.clinicaltrials.gov
Target Information: Thymidine Kinase
Fig. 2 A molecular graphic of the 3D structure of Thymidine Kinase, the blue and the pink portions represent two different molecules, chain a and chain b.
Size: 40930 Daltons
Location: Thymidine kinase (TK) can be found in almost all mammalian cells. Inside a cell, TK is located in the cytoplasm. Thymidine kinase is made during the synthesis phase of the cell cycle. After the protein is produced, it does not disperse throughout the cell initially because it is regulated by an inhibitor called thymidine triphosphate (TTP). Thymidine triphosphate stops the synthesis of thymidine kinase when there is too much of it in the cell. Thymidine kinase is not always present in the cell, it is created when the cell is preparing for division and synthesis.
Function in a normal cell: Thymidine kinase is an important catalyst in the reaction to make thymidine monophosphate. This reaction is represented as: thymidine + ATP ---> thymidine monophosphate + ADP. Thymidine monophosphate goes through another reaction to become thymidine diphosphate, and then another to finally become thymidine triphosphate, the inhibitor of thymidine kinase. The main purpose of these reactions is to introduce thymidine into the DNA, which plays an important role in cell division. Thymidine triphosphate is a required building block for the creation of an extra set of DNA when a cell is preparing to divide.
Drug Information: Ceftriaxone
Schematic figure of drug:
Fig. 3 The 2D structure of Ceftriaxone. Nitrogen is blue, Sulfur is yellow, Oxygen is red, Carbon and Hydrogen are grey.
Formula: C18H18N8O7S3
Molecular weight: 554.571 g/mol
CAS Number: 73384-59-5
Delivery method: injection into a vein
Side effects: pain at injection site, weakness, pale skin, diarrhea, nausea and vomiting, heartburn, rash, stomach bloating, stomach cramps, hemolytic anemia, gall bladder disease, difficulty swallowing, painful or decreased urination, and seizures
Other names: Rocephin, Epinephrine, Biotrakson
Maker or company: Roche
Is it patented?No
Clinical Trials Info: There have been a few clinical trials testing the efficacy of different drugs on the treatment of Salmonellosis. Studies have also been done on the increasing number of drug-resistant salmonellosis strains.
Origin: This drug is a semisynthetic antibiotic that consists of ceftriaxone sodium and is derived from a fungus called Acremonium.
Alternatives to this drug: Zithromax, Flagyl, Docycycline, Azithromycin
Miscellaneous: Ceftriaxone is more active against gram-negative bacteria than gram-positive bacteria
Other uses: sinus infections, endocarditis, Lyme disease, shigella, relapsing fever, typhoid fever, Whipple’s disease, and to prevent infection in certain penicillin-allergic patients